Stable Pharmaceutical Composition Containing Benzimidazole Derivatives and Method of Manufacturing the Same

Abstract

The present invention relates to an inclusion complex containing a benzimidazole derivative with excellent storage stability and a method of its preparation. In particular, the present invention relates to an inclusion complex containing a benzimidazole derivative with improved storage stability and a method of its preparation, where an inclusion complex is manufactured by performing an inclusion reaction by combining a benzimidazole derivative, cyclodextrin and a water-soluble polymer in an aqueous alkali solution in order to be formulated after stabilizing an acid-unstable benzimidazole derivative.

1 . An inclusion complex comprising benzimidazole with improved storage stability wherein a water-soluble polymer is added when a benzimidazole derivative is being included into cyclodextrin and is used in the amount of about 0.1 to 100 parts by weight with reference to 100 parts by weight of said benzimidazole derivative.  
     
     
         2 . In  claim 1 , said benzimidazole derivative is selected from the group consisting of lansoprazole, omeprazole, pantoprazole, timoprazole, picoprazole and rabeprazole.  
     
     
         3 . In  claim 1 , cyclodextrin is used in the amount of about 1 to 5 moles with reference to 1 mole of said benzimidazole derivative.  
     
     
         4 . (canceled)  
     
     
         5 . In  claim 1 , said cyclodextrin is β-cyclodextrin or its derivative.  
     
     
         6 . In  claim 1 , said water-soluble polymer is at least one selected from the group consisting of polyethyleneglycol, polyvinylpyrrolidinon, carboxymethylcellulose, hydroxypropylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose and hydroxypropylethylcellulose.  
     
     
         7 . A pharmaceutical preparation comprising the inclusion complex in  claim 1  and pharmaceutically acceptable ingredients.  
     
     
         8 . The pharmaceutical preparation according to  claim 7 , wherein said inclusion complex is formulated in the form of a tablet or a capsule.  
     
     
         9 . A method of manufacturing an inclusion complex comprising a benzimidazole derivative comprising: 
 a) combining a benzimidazole derivative, cyclodextrin and a water soluble polymer in an aqueous alkali solution; and    b) stirring said mixture at about 20 to 100° C. and adjusting its pH to about 7.0 to 11.0; and    c) cooling down said mixture to about 0 to 30° C., filtering, washing and drying of said mixture to manufacture an inclusion complex.    
     
     
         10 . In  claim 9 , said aqueous alkali solution is selected form the group consisting of alkali metal hydroxides, inorganic or organic alkali salts, amines and a buffer solution.  
     
     
         11 . In  claim 9 , said pH is adjusted by using at least one selected from an organic or inorganic material in the range of about pKa 2.0 to 10.0.